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Altered peptide ligands trigger perforin- rather than Fas-dependent cell lysis
M F Bachmann1, T Ohteki, K M Faienza
1Department of Medical Biophysics, Ontario Cancer Institute, Canada. bachmann@oci.utoronto.ca
Journal of Immunology (Baltimore, Md. : 1950)
|October 31, 1997
Summary
Cytotoxic T lymphocytes (CTLs) use perforin and Fas pathways to kill target cells. This study reveals that altered peptide ligands (APLs) primarily activate the perforin pathway, not Fas, challenging previous findings.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Mechanisms
Background:
- Cytotoxic T lymphocytes (CTLs) eliminate target cells through perforin-dependent and Fas-dependent cytotoxic mechanisms.
- Altered peptide ligands (APLs) have been proposed to selectively engage these distinct CTL-mediated killing pathways.
Purpose of the Study:
- To investigate whether target cells treated with T cell antagonists and APLs are lysed by a specific cytotoxic mechanism (perforin or Fas-dependent).
- To clarify the pathways utilized by CTLs when encountering different peptide ligands.
Main Methods:
- Utilized in vivo and in vitro activated T cells from transgenic mice with a T cell receptor (TCR) specific for lymphocytic choriomeningitis virus.
- Employed T cells from normal and perforin-deficient mice to lyse peptide-pulsed Fas-positive or Fas-negative target cells.
- Differentiated between perforin- and Fas-dependent cytotoxicity.
Main Results:
- Contrary to prior research, target cells treated with T cell antagonists and APLs were predominantly lysed via the perforin-dependent pathway.
- The contribution of Fas-mediated cytotoxicity was comparable between full agonists and APLs.
- APLs did not selectively induce the Fas-dependent pathway.
Conclusions:
- Full agonists, partial agonists, and antagonists trigger similar cytotoxic pathways in target cells.
- The predominant cytotoxic mechanism engaged by APLs is perforin-dependent, not Fas-dependent as previously suggested.